- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03767270
Safety, Tolerability and PK/PD Evaluation of Intravenous Administration of MRT5201 in Patients With OTC Deficiency (STEP-OTC)
September 12, 2019 updated by: Translate Bio, Inc.
A Phase 1/2 Single Ascending Dose Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenously Administered MRT5201 in Subjects With Ornithine Transcarbamylase Deficiency
This Phase 1/2, first-in-human study will evaluate the safety and tolerability of single escalating doses of MRT5201 administered intravenously to subjects with OTC Deficiency (OTCD).
This study will also evaluate the effect of a single dose of MRT5201 on metabolic markers of OTCD and ureagenesis; and determine an acceptable dosing interval of MRT5201.
Study Overview
Status
Withdrawn
Conditions
Intervention / Treatment
Study Type
Interventional
Phase
- Phase 2
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Have a documented diagnosis of OTCD.
- Documented history of ≥1 symptomatic hyperammonemia event with ammonia ≥100 µmol/L
Subject's OTCD is stable as evidenced by meeting the following criteria:
- Ammonia level <175 µmol/L during the Screening Period and at Baseline (Day -1)
- No clinical symptoms of hyperammonemia during the Screening Period and at Baseline (Day -1)
- If using nitrogen scavenger therapy, must be on a stable regimen for ≥28 days prior to signing informed consent
- Subject has maintained a stable protein restricted diet (which may or may not include medical foods) and/or amino acid supplementation with no changes in calorie or protein goals and no changes in medical food and/or amino acid supplementation for ≥ 28 days prior to signing informed consent.
Exclusion Criteria:
- Any laboratory abnormality that may put the subject at increased risk by participating in this study.
Have any significant concurrent or past medical condition that would represent an unacceptable risk to the subject or might jeopardize the collection of high-quality data from the study. These include but are not limited to:
- History of liver transplant, including hepatocyte therapy/transplant
- History of liver disease
- Positive viral serology test results for HIV type 1 or 2 antibodies, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody
- Type I or Type II diabetes that is poorly controlled, in the opinion of the Investigator
- Poorly controlled hypertension (defined as systolic blood pressure [BP] > 150 mm Hg or diastolic BP > 90 mm Hg)
- Use of anticoagulants or platelet inhibitors, including but not limited to heparin and non-steroidal anti-inflammatory drugs (NSAIDS). Acetaminophen is permitted
- Participation in previous clinical studies evaluating investigational OTCD therapies directed at expressing functional OTC protein (eg, OTC gene therapy studies, other mRNA replacement therapy) that has led to the presence of anti-OTC antibodies.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: MRT5201
Single Ascending Low, Mid, and High doses of MRT5201
|
Codon-optimized human ornithine transcarbamylase messenger ribonucleic acid with lipid-based nanoparticles
|
Placebo Comparator: Placebo
Placebo comparator using 5% dextrose in water at the same administration rate as study drug.
|
5% dextrose in water
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The incidence of treatment-emergent adverse events by treatment group
Time Frame: Week 24
|
The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) for each dosing cohort by treatment group, assessed by severity and relationship to study product.
|
Week 24
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetics parameters of MRT5201
Time Frame: 1 month after single dose
|
Pharmacokinetics of MRT5201 as measured by levels of mRNA
|
1 month after single dose
|
Effect of a single dose of MRT5201 on ureagenesis
Time Frame: Up to 1 month after single dose
|
Change from Baseline in 4-hour ureagenesis AUC at weeks 2, 3, 4, and 5 after a single dose of MRT5201
|
Up to 1 month after single dose
|
Effect of single dose of MRT5201 on metabolic markers of OTCD
Time Frame: 6 months after single dose
|
Change from Baseline in 8-hour ammonia AUC
|
6 months after single dose
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
December 1, 2019
Primary Completion (Anticipated)
July 1, 2022
Study Completion (Anticipated)
July 1, 2022
Study Registration Dates
First Submitted
November 28, 2018
First Submitted That Met QC Criteria
December 4, 2018
First Posted (Actual)
December 6, 2018
Study Record Updates
Last Update Posted (Actual)
September 17, 2019
Last Update Submitted That Met QC Criteria
September 12, 2019
Last Verified
September 1, 2019
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Genetic Diseases, Inborn
- Genetic Diseases, X-Linked
- Metabolism, Inborn Errors
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Amino Acid Metabolism, Inborn Errors
- Urea Cycle Disorders, Inborn
- Ornithine Carbamoyltransferase Deficiency Disease
Other Study ID Numbers
- MRT5201-101
- 2018-004095-35 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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